The concentration of glucose and other chemicals and biochemicals can be monitored electrochemically through potentiometry, amperometry or coulometry. (See , for example, Hall, E. A. H., Biosensors, Prentice Hall, N.J., 1991, Chapters 8 and 9). While amperometry requires knowledge of the area of the electrode and coulometry requires knowledge of the liquid volume analyzed, potentiometry does not require such knowledge. In high volume manufacturing, control of electrode dimensions or microcell volumes is of essence, respectively in amperometric or coulometric biosensors, but not in potentiometric ones. The disadvantage of potentiometric devices has been that their output scaled with the logarithm of the concentration of the analyte rather than with its concentration. Consequently, the penalty in potentiometry has been the inability to resolve small changes in concentrations.
Potentiometric assays, unlike amperometric or coulometric ones, do not require accurate definition and knowledge of the area of the measuring electrode or microcell volume. Large scale manufacturing of devices for potentiometric assay, for example of strips for single-use potentiometric self-monitoring of blood glucose concentrations by diabetic patients, would therefore not require the tight control of size, microroughness, or microcell volume that is required for large scale manufacturing of available amperometric, chronoamperometric or chronocoulometric strips. However, the potential increases or decreases usually approximately linearly with the logarithm of the analyte concentration, while the current in amperometry and the charge in coulometry increases usually approximately linearly with the analyte concentration. For this reason, changes in glucose concentration were previously better resolved by amperometry or coulometry than by potentiometry. Also, in large arrays of sensors, such as those produced, for example, through combinatorial processes to have large numbers of different elements, it is necessary to compare the magnitude of signals from different sensing elements. Better resolution of differences between elements of an array, in which not all elements are necessarily of the same size, is enabled through potentiometry, if the potentiometrically derived signal scales about linearly with the concentration of the analyte rather than with the logarithm of its concentration.